Project Summary/Abstract High Speed Detector for LCLS Project Summary/Abstract This proposal aims to bring revolutionary next generation x-ray detector technology to the field of X-ray Free Electron Laser (FEL) based structural biology. X-ray FELs produce extremely short pulses of x-rays which can be exploited to obtain unique information about the structure and the dynamics of biological systems. These short bursts of x- rays allow data to be collected prior to the onset of radiation damage, allowing higher resolution structural information to be obtained compared to more traditional measurements. Additionally, the ultrashort pulses lend themselves naturally to the study of fast dynamics. Combined with data collection under ambient conditions, recently developed X-ray FEL methods of femtosecond crystallography provide unique capabilities to study biological dynamics under physiologically relevant conditions with high spatial and temporal resolution. Even though the fields of femtosecond crystallography and imaging using FEL sources are still fairly young, the detector technology used since the start of operations of the Linac Coherent Light Source (LCLS ) is already outdated and in great need of modernization. A large world- wide effort to develop new detector technology has produced paradigm-changing capabilities that are now available for scientific use. High dynamic range, fast (>2 kHz) detectors with single photon sensitivity and very low noise are now available. Such detectors are specifically designed for the ultrashort pulses from X-ray FELs and can maximize the information collected from the single shots necessary for data collection prior to the onset of radiation damage. This proposal is to purchase a recently available Jungfrau 4M detector which will surpass by more than a factor of ten the repetition rate and the dynamic range of the detector currently used for serial femtosecond crystallography at LCLS, while reducing the noise level. This will greatly improve the performance of LCLS femtosecond crystallography, allowing more access to the facility by providing higher quality data faster. It will also enable fundamentally new capabilities by allowing ever more challenging biological problems to be solved at LCLS, with for example smaller crystals and help make de novo phasing more accessible for the discovery of novel structures. This detector will keep LCLS at the forefront of X-ray FEL biology by continuing to provide a world-leading tool for solving uniquely challenging biological problems that conventional methods cannot solve. This will benefit important areas of research such as metallo-enzymes, membrane proteins, GPCRs and large protein complexes, as well as generally provide more broadly accessible capabilities to study the dynamics of biomolecules. 1